This transgenic mouse model overexpresses wild type human α-synuclein under the regulatory control of the murine Thy 1 promoter. The cellular expression is more widespread compared to the D-Line model, featuring high human α-synuclein mRNA levels in most brain areas. Line 61 mice show abnormal accumulation of human α-synuclein protein in cortical and subcortical regions of the brain, including the substantia nigra. Immunoreactivity is present in both neuronal somata and presynaptic terminals.
Overall expression levels are therefore higher compared to D-Line mice. The Line 61 mouse model is thus well-suited for studies that aim to reduce overall levels of human α-synuclein. Measurable behavioral differences to non-transgenic littermates start at about 2-4 month of age, depending on the behavioral test.
Figure 1: Motor deficits in Line 61 transgenic mice compared to age matched non-transgenic (ntg) littermates. A: Rota Rod of 1 – 6 month old Line 61 mice. B: Pasta gnawing test of 2 – 6 month old Line 61 mice. n = 10-15. Man + SEM; Two-way ANOVA with Bonferroni`s post hoc test. *p<0.05; **p<0.01; ***p<0.001.
Figure 2: Quantification of astrocytosis in Line 61 mice. A: GFAP immunoreactive (IR) area in percent was quantified in the striatum of 6, 9, and 12 month old Line 61 mice and non-transgenic (ntg) littermates. n = 4 per group. Mean + SEM; Two-way ANOVA with Bonferroni‘s post hoc test. *p<0.05. B: Representative images of GFAP labeling in the striatum of 6 month old Line 61 and ntg animals. Scale bar: 50 µm.